Chien Laboratory: At the Forefront of Cardiac Research

JENNA ZHANG

The lab’s approach has led to several breakthroughs. Earlier this year, the lab identified the role of vascular endothelial growth factor (VEGF-A) as a signal that drives endothelial specification of certain progenitor cells.

At the Harvard department of Human Developmental and Regenerative biology, the Chien Laboratory tackles heart disease from the perspective of developmental and molecular pathways. Dr. Kenneth Chien, an M.D.-PhD cardiologist and a professor at the Karolinska Institutet and Harvard University, spoke with Brevia about his lab’s work, including new ways of approaching cardiac disease treatment.

“We started originally using mouse models and more recently have been exploring a way to understand heart disease through the lens of cardiogenesis,” Dr. Chien states. Because there are an insufficient number of heart donors compared to cases of cardiac disease, the use of existing cells as therapy has become increasingly important. Thus, cardiac progenitor cells, special stem cells located in the heart, have great potential as a therapeutic mechanism to treat cardiac disease because of their ability to develop into heart muscle and secrete factors to improve heart function.

In conducting their research, the lab first strives to understand the basics of the type of cells that make up the heart, as well as to identify the signals involved in cardiac cell differentiation and how the development process can go wrong. The lab also utilizes a model system of viewing the heart and its capabilities, an approach that originated with the use of mouse embryonic stem (ES) cells, before moving to human ES cells and human fetal heart tissue. The goal of the subsequent therapy would be to encourage the heart to repair itself by growing new tissue from its own cells, rather than by relying on the injection of massive amounts of mature heart cells. This method eliminates the need to inject any cells into the injured cell and treats heart stem cells as the target of the therapeutic agent, rather than as the therapeutic agent itself.

The lab’s approach has led to several breakthroughs. Earlier this year, the lab identified the role of vascular endothelial growth factor (VEGF-A) as a signal that drives endothelial specification of certain progenitor cells. In a study based upon the VEGF-A discovery, a team of scientists from the Karolinska Institutet and Harvard University determined that the injection of a chemically modified messenger RNA strand, or mRNA, that codes for the growth factor can cause the native stem cells residing in an injured heart to become new coronary vessels instead of cardiac scar tissue. Thus, the repair process stems not from the injection of new cells into the heart, but rather from making a change at the root level: the native heart cells themselves.

For the field of regenerative cardiology in general, Dr Chien indicates that the next step would be to move to a clinical setting to continue testing the use of mRNA therapeutics. New technologies will also need to be developed that can deliver the modified mRNA to cells in the heart. He concludes with final thoughts on the future direction of cardiogenesis research saying that the possibility of studies in primate cardiogenesis may give even more insight into the full potential of heart stem cells as the rapidly developing nature of the research certainly makes for a hot topic in the field of stem cell and regenerative biology and a promising sign of the new capabilities for the medical field as a whole.

Jenna Zhang is a Brevia staff writer. She can be reached at jennazhang@college.harvard.edu.